Adiponectin and the steatosis marker Chi3L1 decrease following switch to raltegravir compared to continued PI/NNRTI-based antiretroviral therapy

Obiageli Offor, Netanya Utay, David Reynoso, Anoma Somasunderam, Judith Currier, Jordan Lake, Obiageli Offor, Netanya Utay, David Reynoso, Anoma Somasunderam, Judith Currier, Jordan Lake

Abstract

Background: People with HIV are at for metabolic syndrome (MetS) and fatty liver disease, but the role of Antiretroviral therapy (ART) is poorly understood. MetS and fatty liver disease been associated with changes in adiponectin, soluble ST2 (sST2), chitinase 3-like 1 (Chi3L1), hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), lysyl oxidase-like-2 (LOXL2) and transforming growth factor β (TGF-β) concentrations in HIV-uninfected populations. Protease (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) may contribute to these comorbidities, but the effects of switching from PI- or NNRTI to raltegravir (RAL) on these biomarkers is unknown.

Methods: Cryopreserved plasma was obtained from a completed, prospective trial of HIV-infected women with central adiposity on NNRTI- or PI-based ART during which they were randomized to remain on their current ART or switch to a RAL based regimen. Biomarker concentrations were quantified using ELISA and Multiplex assays at baseline and 24 weeks after randomization. Wilcoxon-signed rank test evaluated within-group changes, Spearman and linear regression models evaluated correlations between biomarkers and clinical covariates.

Results: Participants had a median age of 43 years, CD4+ T lymphocyte count 558 cells/mm3 and BMI 32 kg/m2; 35% met criteria for MetS. At baseline, higher adiponectin levels correlated with higher Chi3L1 levels (r = 0.42, p = 0.02), as did declines after 24 weeks (r = 0.40, p = 0.03). Changes in sST2 correlated with changes in Chi3L1 (r = 0.43, p = 0.02) and adiponectin (r = 0.40, p = 0.03). Adiponectin and Chi3L1 levels decreased significantly in women switched to RAL vs continue PI/NNRTI.

Conclusion: In women with HIV and central obesity, the hepatic steatosis/fibrosis marker Chi3L1 and adiponectin decrease in conjunction with sST2 decreases following switch to RAL. Whether switching from NNRTI/PI-based regimens to RAL can improve hepatic steatosis and dysmetabolism requires further study.

Trial registration: Clinicaltrials.gov NCT00656175.

Conflict of interest statement

Competing Interests: Judith Currier M.D – Research grant to University of California Los Angeles from Theratechnologies and Merck & Co. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funders had no role in study design, data collection, analysis, interpretation of data, writing manuscript and the decision to publish. There are no declarations regarding employment, consultancy, patents, products in development or marketed products. There are no non-financial competing interests from any author.

Figures

Fig 1. Participant enrollment and disposition.
Fig 1. Participant enrollment and disposition.
Fig 2. Biomarker changes following switch to…
Fig 2. Biomarker changes following switch to RAL vs continued PI/NNRTI.
Fig 3. Biomarker correlations at baseline.
Fig 3. Biomarker correlations at baseline.
Fig 4. Correlations of 24-week changes in…
Fig 4. Correlations of 24-week changes in adiponectin, sST2 and Chi3L1.
Fig 5. Baseline correlations between biomarker levels…
Fig 5. Baseline correlations between biomarker levels & clinical covariates.

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